NIH/NIMH – A Practice-Based Research to Transform Mental Health Care: Science, Service Delivery & Sustainability (U19 Clinical Trial Required)

This Funding Opportunity Announcement (FOA) seeks applications to develop and leverage a practice-based research network (Network) in the United States central to a continuously learning healthcare system and to serve as a national research laboratory to improve mental health outcomes by generating the evidence base that healthcare system decision-makers need. In turn, the healthcare system will drive the research questions based on urgent practice priorities. Studies conducted through this Network will be pragmatic and deployment-focused, incorporating stakeholder perspectives and criteria used for decision making. The goal is to inform, develop, and test interventions and service delivery strategies that are feasible, scalable, and sustainable, and will ultimately improve routine mental health services.

The healthcare landscape in the United States is constantly changing, creating new challenges to the delivery of high-quality treatments and services to children, youth, adults, and older adults with unmet or under-met mental health needs. Epidemiological findings suggest that approximately one-half of the United States population meets lifetime criteria for a mental disorder, and approximately one-quarter of the population meets criteria in any given year. However, only one-half of people with any mental health disorder and only two-thirds of people with a serious mental health disorder received mental health services in the previous year. Of those that find their way into mental health care, many fall out of care and/or do not receive guideline-concordant treatment. Documented disparities in access, quality, and outcomes of treatment and services (e.g., in racial, ethnic, sexual, and gender minority communities, and/or rural populations), a fragmented healthcare system, provider shortages, healthcare affordability, and other factors moderate these findings.

While investments in research have generated potential solutions to many of these challenges, that research has little public health impact if findings do not influence actual healthcare practice.  This outcome is especially common when research questions, strategies for addressing those questions, and methods for disseminating and implementing research findings are not embedded in healthcare practice.  Moreover, the cost of individually conducting large-scale pragmatic and/or comparative effectiveness trials and other research can be prohibitive without a common infrastructure that can be leveraged.

Practice-based research networks have robust infrastructures that can be leveraged to (1) efficiently and rapidly identify, recruit and enroll large and diverse patient populations into effectiveness trials; (2) harmonize electronic health record (EHR) data across multiple integrated systems for common analyses; (3) build capacity for the collection, storage, and analysis of biologic and/or genetic material; (4) study low base-rate events (e.g., suicide, autism spectrum disorders, first episode psychosis) by using and advancing innovative methodologies (e.g., predictive analytics); (5) develop, test, and deploy large-scale mental health information technology (IT) interventions, workflows, and decision support systems; (6) develop and test strategies to address health disparities; and (7) generate data that will fuel the transformation of mental health care.

NIMH recognizes the importance of such networks and directly calls for researchers to leverage such partnerships when designing high impact studies. See https://www.nimh.nih.gov/about/strategic-planning-reports/strategic-research-priorities/srp-objective-4/index.shtml for details.

An innovative and robust research infrastructure within large, representative healthcare settings may facilitate capacity for pragmatic, generalizable research that yields effective and efficient strategies for care.  As NIMH’s prototype of a continuously learning healthcare system, the practice-based research Network will be embedded within one or more integrated (public and/or commercial) healthcare settings serving large and representative patient populations, including people with severe mental illness, and including settings offering evidence-supported integrated care (e.g., collaborative care and/or coordinated specialty care) across the United States. The Network will leverage and enhance a sophisticated infrastructure for research to be prioritized, conducted, and utilized by the affiliated healthcare system(s).  Research on topics with relatively low incident cases (e.g., suicide, first episode psychosis, and autism spectrum disorder) and research which takes advantage of and improves upon (1) harmonization of common data elements, (2) EHR phenotyping, and (3) systematic procedures for rapid case finding, participant recruitment, eligibility determination, and assessment can be more easily conducted on such a Network.

General Requirements

The Network is expected to function as a resource to the broad mental health research community, and its impact will be assessed through achievement of the following activities:

• Maintaining accessibility to relevant patient, provider, and health system data;
• Facilitating and coordinating access to these data for research conducted by Network-affiliated and non-affiliated investigators using approaches and solutions that optimize the use of the Network and are conducive to collaborative efforts;
• Maintaining high levels of expertise and competency in scientific areas relevant to the Network, US healthcare system stakeholders, and federal, state, and other key stakeholders;
• Facilitating interactions and research collaborations among (non-Network affiliated) mental health researchers who might benefit from these data;
• Increasing participation of Network-affiliated and non-affiliated investigators in independently funded research, including efforts to increase the number, scope, and scientific impact of research projects conducted by external investigators in collaboration with the Network;
• Building from established relationships with relevant constituent groups (e.g., patients, providers, administrators, payors, relevant federal and state agencies) to inform research questions, and attending to front-end infrastructure to secure stakeholder commitment to adopt, implement and sustain successful practices and products developed within this Network;
• Developing and testing strategies (using implementation science) to encourage adoption, quality, scale-up, and sustainability of new innovations and existing best practices;
• Developing and maintaining capacity to rapidly respond to and address urgent questions from Network-affiliated healthcare system partners, as well as federal, state, and other key stakeholders;
• Advancing expertise in research methodology and “big data” science, with attention to implementing findings from these advances into routine practice;
• Conducting two (2) well-powered Signature Projects (described below), one of which must be a large-scale pragmatic trial to definitively answer a research question of high importance and impact and whose findings, whether positive or negative, will be used by the Network’s healthcare system(s) to improve practice in an identifiable and measurable way;
• Conducting two (2) Pilot Projects (described below) of high importance to Network stakeholders that will allow Network and external investigators to develop competitive applications to support larger-scale research projects;
• Conducting clinical trials of interventions that include therapeutic (pharmacotherapies or psychosocial interventions), preventive, or services interventions;
• Ensuring that one (1) of the four (4) projects (i.e., either one of the two required Signature Projects or one of the two required Pilot Projects) is specifically designed to reduce racial, ethnic, sexual, and/or gender minority disparities in mental health status, service utilization, and/or treatment outcomes;
• Facilitating additional pilot feasibility research through a process for soliciting, reviewing, selecting, and supporting the conduct of promising pilot feasibility projects that can be completed within the project period.
• Including mid-career investigators in positions of leadership and fostering the careers of young investigators;
• Creating and demonstrating efficiencies in the Network business processes and in the Signature Projects (described below) compared to conducting studies de novo.
• Developing and utilizing simulation approaches to model the potential public health impact of implementing research informed approaches and guide decision making; and
• Harnessing perspectives from end-user stakeholders and from new and emerging fields (e.g., health information and communications technology, health systems engineering, decision science, behavioral economics) to transform clinical research and practice.

It is expected that by the end of the proposed funding period, investigators involved in the Network-sponsored research (including outside collaborators) will have collectively submitted a minimum of five (5) investigator-initiated research project applications, to include R01, R34, R21, and/or R03 applications.

This practice-based research Network for mental health will capitalize on the successes of and lessons learned from other such networks in mental health and other disease areas.

Overall Structure of the Network

To ensure efficient conduct of the activities outlined above, the proposed practice-based research network structure will be comprised of an Administrative Core and a Methods Core, as follows:

The Administrative Core will have three functional Units:

1. The Organizational Unit will coordinate the Network’s administrative functions including, but not limited to, coordinating and implementing administrative functions, including interactions among Network members and providing organizational support for joint Network activities (e.g., organizing meetings, teleconferences, etc.). The Organizational Unit (with input from the other Administrative Core Units and the Methods Core) will also coordinate the evaluation of the Network’s research activities, efficiencies created by the Network infrastructure, and the public health impact of the Network’s activities. This formative evaluation data will be utilized to iteratively refine the Network’s ongoing quality improvement activities and inform plans for future collaborative research.
2. The Outreach and External Collaboration Unit is expected to promote the Network as a resource to external investigators and to healthcare systems by cultivating new collaborations, facilitating access to Network resources by external investigators, and by supporting the implementation of Network findings within partnering and other health systems. Importantly, this Unit must serve a liaison function to help connect non-Network-affiliated investigators with Network investigators who would be most appropriate as potential consultants and/or collaborators. This Unit must also establish an efficient system and operating procedures for receiving, vetting, and managing requests for access to data, ideas for collaborations, and applications for research projects from the scientific community, and for supporting training experiences for junior investigators. Finally, this Unit must promote outreach to and communication with member and external health system operations, to facilitate the identification of new research topics for study and to promote the integration of findings and research-generated products into health system operations. This final function will include dissemination of research products, including assessment/intervention approaches and materials, methodological/analytic approaches, common source programming for technology-assisted approaches, and de-identified data for integration/re-analysis.
3. The Emerging Issues Unit will develop a rapid and systematic capability for response to real-time inquiries to policy and practice relevant requests from Network leaders, as well as federal, state, and other stakeholders. These rapid responses will include data pulls and data analyses from Network healthcare systems. This capacity will include a transparent process to vet and prioritize requests, clarify the key question(s) being asked, determine requirements needed to fulfill the request, and develop the format and timeline for a response.  The Emerging Issues Unit will provide a rapid evidence brief that is responsive to the stakeholder inquiry. The application should include the capacity for vetting and prioritizing research topics, consistent with the following criteria:

Topic nominated by system-level leadership: the proposed rapid response will be incorporated into health system decision-making and is likely to make a significant impact (e.g., clinical guidelines, formulary guidance, resource allocation, or research agenda development).

Significant issue for Network leadership or key federal or state stakeholders: the topic represents important uncertainty for decision makers (e.g., benefits/harms, variation in care, new emerging technology, or controversy) and will help resolve health care dilemmas.

Not duplicative: the topic is not already covered by an available or soon-to-be available high-quality review by VA, AHRQ, or other organization.

Feasible: data to inform the review should be available within the Network’s data infrastructure and the published literature.

Engaged operational partner: nominator of the proposed review has been responsive and engaged during the topic development phase and has provided timely input regarding the proposed scope.

The Methods Core will have two functional Units:

1. The Informatics Unit comprises the Network resource function. This Unit should be organized to support the Network informatics infrastructure, including a data warehouse, and to develop and implement improvements in data collection methods and capacity, informatics tools, etc. The Informatics Unit should coordinate informatics-related efforts at individual Network member sites as well as interact with other Units and Projects (see below) to support their functions.
2. The Scientific Analysis Unit should be organized to generate new methodology and analytic/computational approaches and to apply state-of-the-art approaches from the fields of big data science, health services research, and implementation science. The Unit should facilitate the development and implementation of the Network’s Signature and Pilot Projects, and the Network-affiliated research, in general.

Signature Projects (2)

The Signature Projects should address a significant problem in the prevention, treatment, management, and/or the delivery of services to people with mental disorders served by the health systems affiliated with the Network.

Signature Projects might involve effectiveness research aimed at refining and optimizing preventive and therapeutic interventions; effectiveness research testing services interventions that target patient-, provider-, or systems-level factors in order to improve service use, care delivery, and/or outcomes; or mental health services research that is consistent with NIMH’s Strategic Plan, but is not immediately focused on development and testing of services interventions, including studies to identify and elucidate mutable factors that impact access, utilization, quality, financing, outcomes such as disparities in outcomes, or scalability of mental health services.

At least one (1) of the two (2) Signature Projects must be a clinical trial. The projects should align closely with NIMH Strategic Research Priorities, and the topic should be demonstrated to be of such value to the affiliated healthcare system(s), such that, a priori, there is a well-developed plan for how definitive findings (whether they are positive or negative) will inform practice. For example, if the findings are positive, how will the intervention be adopted, sustained, and/or scaled once the project period ends?  Conversely, what practices will be changed or de-implemented should findings be negative? Projects should be designed such that whether findings are positive or negative, the findings will also inform future research directions (e.g., intervention optimization, empirically informed adaptations for refractory groups, refinements to facilitate implementation).

To be responsive, any projects that involve a clinical trial must follow the NIMH experimental therapeutics approach and applicants are strongly encouraged to review related information about this approach (http://www.nimh.nih.gov/about/director/2012/experimental-medicine.shtml and https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-17-608.html). Consistent with the NIMH experimental therapeutics approach, tests of intervention effectiveness or service delivery approaches should explicitly address whether the intervention engages the proximal target(s)/mechanism(s) presumed to underlie the intervention effects (the mechanism that accounts for changes in clinical/functional outcomes, changes in provider behavior, etc.) and explicitly examine whether intervention-induced changes in the presumed targets are associated with clinical benefit. In this manner, the results of the effectiveness trial will advance knowledge regarding therapeutic change mechanisms and inform decisions about whether further testing or implementation is warranted (see NIMH web page on Clinical Trials).

Signature Projects that involve a pragmatic clinical trial should be designed as a hybrid effectiveness-implementation clinical trial Type I, II, or III, depending on the level of pre-existing effectiveness evidence and implementation readiness. A comparison group (or groups) should be chosen so that findings will be interpretable in terms of public health impact, clinical significance, and/or readiness for intervention implementation within the Network and in the general community practice setting.

One of the two Signature Projects *or* one of the two Pilot Projects (described below) should be designed to reduce disparities in mental health status, services utilization and/or treatment outcomes.

The Scope of research for Signature Projects should be as follows:

• The research question(s) should be of major importance to people with mental disorders, and the interventions/approaches that are proposed for testing should have the potential to result in substantial functional and/or systemic improvements.
• The projects should exploit efficiencies made available by the practice-based research Network (e.g., potential trial participants can be identified and enrolled via EHR; primary endpoint events can be easily and objectively operationalized using routinely collected data (e.g., hospitalization, emergency department visits)).  As such, there should be dramatic and demonstrable efficiencies created, which will be reported in the evaluation coordinated by the Administrative Core, compared to if the study was conducted de novo, without leveraging Network infrastructure.
• The projects should be adequately powered to definitively answer primary research questions and detect strong signals (even if not definitive) related to treatment optimization for a variety of selected subpopulations (e.g., populations at risk for suicide, of different ages; of different racial-ethnic backgrounds; with different health literacy levels; with medical, mental health, or substance use comorbidities; and/or with expected challenges related to engagement, adherence and continuity of care).
• Project designs should maximize external validity of the study by testing the generalizability of findings across distinct health care settings and diverse staff and patient populations, with explicit a priori hypotheses about disparity populations and disparity settings.

For Projects that involve Clinical Trials:

• The clinical trial should test and compare interventions (which can involve service delivery approaches, therapeutic or preventive interventions (e.g., pharmacotherapies, psychosocial interventions), or policy or organizational changes) that apply broadly to patient populations and are suitable for use in multiple health systems, with the broad goal of determining whether the intervention improves health outcomes and adds value to the use of the nation’s health care resources.
• The intervention(s) should be scalable, such that they could be implemented with fidelity by clinical providers or other staff typically found in the health care setting (not just those with exceptional levels of training or competence) or could be self-administered through computer-based technology with appropriate assessments of quality and utilization.
• As appropriate, project designs will incorporate rigorous and robust comparison conditions, with trial participants prospectively assigned to study conditions within the health care systems.
• The clinical trial must adhere to NIMH’s experimental therapeutics paradigm. The clinical trial will be considered especially innovative if measurements of targets (i.e., mechanisms) can occur in an automated manner or with minimal burden to research participants.

Pilot Projects (2)

The two (2) Pilot Projects should propose innovative approaches consistent with the goals of this current announcement and the NIMH Strategic Research Priorities.  The Pilots should seek to optimize and improve care for a diverse population of patients within defined healthcare systems of the Network; develop and/or test new IT platforms, risk algorithms, decision support systems, and preventive, therapeutic (to include pharmacotherapies), or services interventions; create efficiencies in all aspects of the conduct of research, dissemination of findings, and produce study results that can directly inform practice change; reduce health disparities by engaging intervention targets; and/or improve methodologies in systems research, and/or seek strategies to continuously improve the accessibility, quality, continuity, equity and value of services delivered within the Network.  The general scope of research and the questions addressed by these Pilots should be modeled on the NIMH R34 mechanism for clinical trials (https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-18-706.html) and/or non-trial services research (https://grants.nih.gov/grants/guide/pa-files/PAR-18-267.html).

At least one Pilot must be a clinical trial. For any Pilot that is a clinical trial, the NIMH experimental therapeutics paradigm must be followed and research questions should be similar in type and scope to those supported by the NIMH R34 mechanism.

One of the two Pilot Projects *or* one of the two Signature Projects (described above) should be designed to reduce disparities in mental health status, services utilization and/or treatment outcomes.

Additional pilot feasibility research:   In addition to the Signature and Pilot Projects, the Network is intended to facilitate emerging opportunities for additional pilot feasibility research through a process for soliciting, reviewing, selecting, and supporting the conduct of promising pilot feasibility projects of 1-2 years duration, similar in scope to an NIH R03 grant mechanism, that can be completed within the project period. Accordingly, the scope of science should include such pilot feasibility projects that can be proposed by new or established investigators to address innovative, interdisciplinary research that is consistent the Network’s focus, in order to position the investigator(s) for subsequent research that aligns with the Network’s program of research. Pilot feasibility projects should involve Network-affiliated as well as non-affiliated investigators, wherever possible.

It is expected that by leveraging the infrastructure of the Network and the healthcare systems, dramatic and demonstrable efficiencies will be created compared to similar studies conducted de novo.

Markers of Successful Practice-Based Research Network

A successful Network will accomplish the following tasks within the period of the award:

• Build and extend the capacity of the Network to conduct prospective trials via the successful completion of pilot studies of interventions not yet studied in such networks.
• Enhance the quality, type, and analysis of data within the EHR (to include biologic and/or genetic data) which will ultimately improve the delivery of mental health services in routine practice.
• Successfully complete:  two (2) Signature Projects of high impact on the mental health and functioning of a large population, where positive or negative findings will lead to measurable improvements in practice across the Network sites; two (2) Pilot Projects; and, additional pilot feasibility studies that position the investigator(s) for subsequent research that aligns with the Network’s program of research.
• Develop and submit at least five (5) investigator-initiated applications for research that will leverage Network infrastructure. Involving outside investigators in these applications is strongly encouraged.
• Expand tools to create efficiency in the rapid conduct and replication of effectiveness, services, and implementation research studies on the Network.
• Use business models which foster data sharing and collaboration with non-Network researchers and strengthen the self-sustainability of the Network.
• Benchmark the costs and document efficiencies associated with conducting a range of studies on the Network, as compared to traditional approaches to launching and conducting research.
• Successfully disseminate trial results to health system partners resulting in significant change of policy and/or practice as a direct result of study findings.
• Expeditiously disseminate primary and secondary outcomes in high-quality journals consistent with NOT-OD-16-149 and NOT-OD-18-011.
• Disseminate Network generated research products, including methodological/analytic approaches, assessment and intervention approaches and materials, sharable programing (e.g., for technology-based applications), and de-identified data.
• Reduce disparities in mental health status, service utilization, and treatment outcomes in the health of people with mental illness, including disparities in medical comorbidities among adults with serious mental illness and youth with serious emotional disturbance.
• Harmonize data systems with commercial and/or public healthcare systems that are providing services to diverse populations for the purposes of research and continuous quality improvement associated with a learning mental health healthcare system.
• Include individuals who are insured through commercial plans, Medicaid, and who are uninsured but are treated in commercial and/or public healthcare systems.  Networks that include public healthcare systems are strongly encouraged.”

Deadline:  February 28, 2019 (full proposal; letter of intent due 30 days prior to deadline)

URL:  https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-19-225.html

Filed Under: Funding Opportunities